Research Collaboration Protein Diagnostics
Intelligent Blood Sensors
A new device is revolutionizing blood analysis. Developed by Siemens Dematic in cooperation with Leipzig-based pes Diagnosesysteme, the device provides on-the-spot analysis of the concentration of up to eight proteins at the same time. In conjunction with special analytic software, it can also help doctors make a diagnosis on the basis of the ratio of specific marker proteins present in the blood.
At the heart of the new sensor is a plastic prism with a micro-reaction chamber. Bottom: monitoring production in a pes cleanroom
Physicians who want to do a blood test almost always have to send off a sample to a lab. Now, however, there's a new device that offers rapid point-of-care testing. Developed by Siemens Dematic for start-up pes Diagnosesysteme of Leipzig, Germany, the unit comprises a fully automatic laboratory in mini format. In just a few minutes, it can analyze proteins in the blood with all the accuracy of a full-scale lab. What's more, the new system is highly versatile. Not only can it analyze up to eight individual values at once, but it can also calculate a patient profile on the basis of the concentration of specific proteins, which can help doctors to reach a more accurate diagnosis. Whether checking for a coronary or an inflammation, an infection or a tumorthe new system can be tailored to a range of medical conditions.
In order to measure proteins, laboratories analyze the reactions between antibodies and condition-specific antigens. It can take several hours to deliver a reliable result. "Our goal was to achieve a faster diagnosis," says Thomas Löser, CEO and founder of pes. A chemical process engineer, Löser developed software for analyzing a combination of proteins. With the help of eight tumor markers, he was able to determine whether a patient had lung cancer and how far the tumor had advanced. The problem was that the samples could only be processed by Löser's staff at company headquarters in Leipzig, Germany. That meant doctors had to prepare precise samples and send them to Leipzig in special refrigerated containers"a logistical nightmare," as Löser admits. Moreover, it took a number of days to produce a result. "We came to the conclusion that we would have to provide the customer with an onsite device," he says. The solution was to use an optical detection method from the ICB Institute of Chemical and Biosensorics in Münster, Germany, which combines protein analysis and a mathematical evaluation.
Although this may not sound too challenging, the system is actually the product of a finely tuned interplay between molecular biology, microfluidics, mechanics, electronics, highly sensitive excitation and detection optics, and software for control and analytic functions. In his search for an interdisciplinary team capable of putting together such a system, Löser turned to the mechoptronics specialists at Siemens Dematic in Munich. Within three months, the group had come up with functional specimens that demonstrated that the optical detection method worked. "After that, we took over development of the analysis system," says Franz Drobner, head of Devices & Sensor Development. Now ready to go into production, the technology is being financed partly by Siemens Medical Solutions and partly from a venture capital fund known as the Sächsischer Beteiligungsfonds.
The system comprises a detection device slightly bigger than a laptop, and disposable plastic sensors about the size of a human thumb. The device mechanically controls the analytical process, optically registers the data and prepares it for further computer processing. A highly complex biochemical micro-reaction takes place in the sensors (see ? box). In addition, each sensor contains a chip that tells the unit which special program is running and how the data is to be evaluated.
"Gaining approval for the system is the next major hurdle," says Löser. "Experts from Siemens Medical Solutions are helping here, since they have more experience in this area." Before being approved as an in vitro diagnostic appliance, the unit must, among other things, analyze more than 1,500 patient samples in the context of a clinical study. The device is to be marketed by Jaeger of Würzburg, Germany, under the name MultiCheck. The company, which has extensive experience in the field of small diagnostics equipment, became part of the Philadelphia, Pennsylvania-based Viasys Group last year. The first sensors to hit the market will measure the so-called c-reactive protein (CRP), levels of which increase in the blood as a result of inflammations and surgery, as well as marker proteins indicating coronaries, cancer of the prostate and pneumonia.
Although the analysis only takes a few minutes, Löser still regards the method as too slow for some applications. After all, in the event of a coronary, every minute counts. Löser therefore plans to modify the unit to enable it to produce a provisional warning if the values in a coronary-specific marker protein analysis indicate a coronary.
Norbert Aschenbrenner
Complex Biochemistry in a Miniature Laboratory
To perform a test, a doctor simply puts some blood in the opening of the sensor, inserts it into the device, and presses the start button. A small pump moves the blood across a membrane within the sensor. This separates the red blood platelets from the plasma, which contains the proteins to be analyzed. Just under four microliters of plasma are transferred by the pump to a special chamber, where the proteins react to form a complex (1) with specific antibodies that carry fluorescent dyes visible under laser light. The pump then forces the mixture onto a prism. Arranged in parallel on this prism are test strips containing further specific antibodies (2), which capture and fix the marked protein complexes at precise places (3). A laser now scans across the prism. Due to optical laws governing total internal reflection, only those dyes bound to the protein complexes on the surface of the prism are excited by the laser into giving off light. A special detector registers the fluorescence (4). By contrast, any other antibodies in the solution do not give off light. The intensity of the fluorescence offers a measure of the concentration of the marker protein. The system does not wait until the fluorescence of a strip has developed its full intensity. Instead, it measures the increase in intensity over time (5) and calculates the final concentration on this basis. The entire testing procedure lasts a maximum of 15 minutes.
